Cardiovascular disease is the third highest among the ten leading causes of death for people in Taiwan, following cancer and cerebrovascular disease. Coronary atherosclerosis isone of the main factors that cause cardiovascular disease and is a slow and complicated process. The reason for such occurrence includes the migration of smooth muscle cells to the cardiovascular intimal layer and smooth muscle cell proliferation. This narrows and blocks the blood vessel and leads to myocardial ischemia, myocardial necrosis (myocardial infarction), angina pain (angina pectoris), or even leads to heart failure, cardiogenic shock, or sudden cardiac death.
Cardiovascular disease can be treated by pharmaceutical drugs. Common pharmaceutical drugs include anticoagulants (such as Coumadin), antiplatelet agents (such as aspirin), vasodilators (such as Isordil), hypolipidemic drugs (such as Statins), etc. However, the effect of the drug therapy is slow and limited, and therefore, patients with more severe symptoms are in general treated in combination with surgery. The most commonly seen surgery includes balloon angioplasty, stent implantation, and coronary artery bypass surgery. Balloon angioplasty often is used in conjunction with stent implantation. However, the process of the balloon angioplasty and stent implantation, as well as the balloon and stent themselves, can damage the blood vessel, which leads to inflammation of the blood vessel tissue and the release of cytokines and growth factors, causing smooth muscle cells to migrate to the blood vessel intimal layer and proliferate, and thus results in blood vessel restenosis. Blood vessel restenosis not only greatly reduces the surgery treating effect but also exacerbates the symptom of cardiovascular stenosis. Thus, there is still a need for a method or drug to inhibit cardiovascular stenosis effectively or even inhibit cardiovascular restenosis after surgery in the treatment of cardiovascular diseases to solve various problems that exist with the known therapeutical method.
During the research and development (R&D) of cardiovascular drugs, cell tests or in vitro tests are usually first performed to screen out a compound with the most medicinal potential to obtain a preliminary successful R&D result in this stage. However, it is well-known that in most circumstances, the compound with the most medicinal potential usually cannot pass the following in vivo tests in the animal body, and thus the compound cannot be used in clinical treatment. Hence, despite the numerous compounds that have been deemed to have treatment effects for cardiovascular diseases (such as those disclosed in Taiwan Patent Publication No. 234086, No. 390876, No. 391964, and No. 403650, etc., which are incorporated hereinto by reference), only few cardiovascular drugs can be really used clinically in the market. This explains why the preliminary result of in vitro tests cannot guarantee to obtain the same successful result as in vivo tests.
The inventors of the present invention found that through the in vivo tests, n-butylidenephthalide can effectively inhibit the growth of smooth muscle cells in the animal body, and further inhibit cardiovascular stenosis, or even inhibit the restenosis after surgery. Therefore, n-butylidenephthalide can be used to treat cardiovascular diseases.